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Solution phase titrations are made easy by multi-nuclear FlowNMR spectroscopy with automated, continuous titre addition to give accurate insights into Brønsted acid/base, hydrogen bonding, Lewis acid/base and metal/ligand binding equilibria under native conditions.

Noyori-Ikariya type [(arene)RuCl(TsDPEN)] (TsDPEN, sulfonated diphenyl ethylenediamine) complexes are widely used C=O and C=N reduction catalysts that produce chiral alcohols and amines via a key ruthenium-hydride intermediate that determines the stereochemistry of the product. Whereas many details about the interactions of the pro-chiral substrate with the hydride complex and the nature of the hydrogen transfer from the latter to the former have been investigated over the past 25 years, the role of the stereochemical configuration at the stereogenic ruthenium center in the catalysis has not been elucidated so far. Using operando FlowNMR spectroscopy and nuclear Overhauser effect spectroscopy, we show the existence of two diastereomeric hydride complexes under reaction conditions, assign their absolute configurations in solution, and monitor their interconversion during transfer hydrogenation catalysis. Configurational analysis and multifunctional density functional theory (DFT) calculations show the λ-(R,R)SRu configured [(mesitylene)RuH(TsDPEN)] complex to be both thermodynamically and kinetically favored over its λ-(R,R)RRu isomer with the opposite configuration at the metal. Computational analysis of both diastereomeric catalytic manifolds show the major λ-(R,R)SRu configured [(mesitylene)RuH(TsDPEN)] complex to dominate asymmetric ketone reduction catalysis with the minor λ-(R,R)RRu [(mesitylene)RuH(TsDPEN)] stereoisomer being both less active and less enantioselective. These findings also hold true for a tethered catalyst derivative with a propyl linker between the arene and TsDPEN ligands and thus show enantioselective transfer hydrogenation catalysis with Noyori-Ikariya complexes to proceed via a lock-and-key mechanism.

Process analytical technology (PAT) is an umbrella term that covers a range of tools and is often cited as being an important component of other innovative initiatives, such as quality by design, real-time release, and continuous manufacturing. PAT has brought together different disciplines, which was presumably one of the intentions of the Food and Drug Administration guidance “PAT- A Framework for Innovative Pharmaceutical, Development, Manufacturing and Quality Assurance.” PAT has different connotations within different industries, companies, and health authorities. Each company selects tools, vendors, integration with hardware and software, and how (or if) to communicate to Health Authorities. Different approaches to PAT can be used to achieve the same objective and depend on company internal factors, which have led to diversity of approach across the industry. This chapter includes a description of general strategies by development phase as well as the primary drivers for deployment of PAT.

Transfer hydrogenation of acetophenone from formic acid/triethylamine mixtures catalysed by the Ikariya–Noyori complex [(mesitylene)RuCl(R,R)-(TsDPEN)] has been investigated using simultaneous high-resolution FlowNMR and FlowUV-Vis spectroscopies coupled with on-line sampling head-space mass spectrometry and chiral high-performance liquid chromatography using an integrated, fully automated recirculating flow setup. In line with previous observations, the combined results show a gradual switch from formic acid dehydrogenation to hydrogen transfer mediated by the same Ru-hydride complex, and point to a Ru-formate species as the major catalyst intermediate. Hydrogen bonding in the formic acid/triethylamine mixture emerges as a sensitive 1H NMR probe for the transfer hydrogenation activity of the system and can be used to locate optimum reaction conditions.

Jo Ann McLaughlin was born in Rainhill, Merseyside, to Millie and Jim, an American. The family moved out to the USA when Jo was 2 years old; they lived in Rhode Island and Washington. With her mother unable to settle, Jo and her younger sister, Sue, returned to Widnes when Jo was 5. Joined by their father a year later, the family moved to Surrey and three years later to Swindon. When Jo was 12, they all moved back to Merseyside, where, to her delight, Jo’s youngest sister, Jayne, was born. Jo had found the many school moves hard, but she was now able to enjoy …

HIV Introduction Human immunodeficiency virus (HIV) is a retrovirus acquired by direct inoculation of infected bodily fluids. This is most often during sexual intimacy, but may also result from contaminated needles or iatrogenic interventions, such as blood transfusion or surgical procedures with contaminated products. The infection is lifelong and if untreated significant morbidity and mortality arise from HIV-associated infections and malignancies; this is termed the acquired immune deficiency syndrome (AIDS). During infection, HIV enters cells presenting CD4 receptors, the most common being the CD4+ T lymphocyte. Within the hosting cell, HIV replication, virion release and eventual cell death occur. The main measurable and prognostic parameters widely used are quantification of peripheral CD4 cells (the CD4 count), and the level of viraemia (HIV viral load). The likelihood of AIDS-defining illness developing increases with progressive CD4+ cell depletion, which occurs steadily over time from infection and more rapidly in individuals with a higher HIV viral load. The advent of highly active antiretroviral therapy (HAART) in the late 1990s transformed the management of HIV-positive patients, and the infection is now generally treatable with a good prognosis, particularly when detected early. In addition to this, effective HAART together with appropriate obstetric management, infant antiretroviral prophylaxis and avoidance of breastfeeding has reduced rates of mother-to-child transmission (MTCT) of HIV significantly. Universal screening for HIV in UK antenatal clinics from 1999 onwards, followed by appropriate management of mothers and their babies, has resulted in MTCT rates falling from between 20–30%, depending on maternal viral load in the mid-1990s to less than 1% in 2010. Worldwide, of the 34 million people living with HIV, 69% reside in sub-Saharan Africa, with other high-prevalence areas including Asia, the Caribbean and Eastern Europe. Many HIV-positive parturients receiving their antenatal care in the UK have acquired HIV whilst residing in one of the pandemic areas. The estimated UK prevalence in 2009 was 2.2 per 1000 women giving birth; most of these live in urban areas, with London having the highest rates. Effect of HIV on pregnancy HIV infection itself does not cause sub-fertility, although HIV-positive women may have decreased fertility due to associated conditions such as concurrent infections or illnesses, opiate use and low weight. HAART itself, particularly protease inhibitors, has been associated with preterm delivery in some studies, but not in others.

This paper examines assistance provided by the UK government over the last decade to the police in developing countries. It begins with an outline of the way in which this assistance has developed, discussing the rationale underlying policies. It then looks at the difficulties involved in promoting and supporting the implementation of forms of policing that seek both to achieve greater police-community partnership and to fulfil the wider policy objectives of the Department for International Development, namely democratisation, enhancement of human rights and poverty elimination. It concludes that, despite some successes in rebuilding police forces in post-conflict situations, the overall objectives of achieving greater protection for the poor and vulnerable have been undermined, by treating the police in isolation from other parts of the justice system and by the failure to develop inclusive, working partnerships with civil society.